Thrombospondin-1 is a potent inhibitor of angiogenesis (for a review, see Dawson, D. W. and Bouck, N. P., “Thrombospondin as an inhibitor of angiogenesis,” In: B. A. Teicher (eds.), Antiangiogenic Agents in Cancer Therapy, pp. 185–203, Totowa, N.J.; Humana Press, Inc., 1999). It inhibits endothelial cell growth, migration and tube formation in vitro (Panetti, T. S., et al., J. Lab. Clin. Med., 129: 208–216, 1997). In vitro assays have shown that platelet thrombospondin-1 is involved in thrombosis, fibrinolysis, wound healing, inflammation, tumor cell metastasis and angiogenesis. The major form of thrombospondin secreted by platelets and endothelial cells is TSP-1. Thrombospondin-1 (TSP-1) is an angiogenesis inhibitor. Thrombospondin-1 has three copies of the TSR. TSP-1 is a trimeric molecule. Thus, the fully assembled protein contains nine TSRs.
The ingrowth of new capillary networks into developing tumors is essential for the progression of cancer. As pointed out in a review by Folkman (Folkman, J., Proc. Natl. Acad. Sci. USA 95: 9064–9066, 1998), antiangiogenic therapy has little toxicity, does not require the therapeutic agent to enter tumor cells or cross the blood-brain barrier, controls tumor growth independently of growth of tumor cell heterogeneity, and does not induce drug resistance. Thus, the development of pharmaceuticals that inhibit the process of angiogenesis or can inhibit abnormal cell proliferation by other mechanisms is an important therapeutic goal.